TEV-48125 took effect within days

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An investigational calcitonin gene-related peptide (CGRP) inhibitor for chronic migraine may start to work within 3-7 days, depending on dosage, according to a post-hoc analysis of phase IIb data.

Note that the biggest study limitation was lack of follow-up with patients to determine whether the early-onset effect was clinically meaningful.

An investigational CGRP inhibitor for chronic migraine may start to work within days, researchers reported.

In a post-hoc analysis of data from a phase IIb trial, patients saw significant declines in the number of headache hours starting as soon as 3 days after the higher 900-mg dose (P=0.048) and 7 days after the lower 675/225-mg dose (P=0.033) of TEV-48125, Marcelo Bigal, MD, PhD, of Teva Pharmaceuticals, and colleagues reported online in Neurology.

"In the current paper in Neurology, we expanded the analyses and the data suggests that TEV-48125 was provided relief even faster than we believed," Bigal said in an email to MedPage Today. "To my knowledge, this is the fastest separation ever demonstrated in [chronic migraine]."

The original study enrolled 261 patients at 62 headache centers and other sites across the U.S. who were randomized to one of three groups: 900 mg once a month for 4 months; an initial 675-mg dose followed by three monthly 225-mg doses; or placebo injections each month for 4 months.

The researchers previously reported that reduction in mean headache hours was greater for those on either the high dose (-67.5 hours, P=0.006) or low dose (-59.8 hours, P=0.039) of the drug compared with those on placebo (-37.1 hours).

In the new post-hoc analysis, they found that the higher dose separated from placebo after 3 days (-3.08 hours versus +0.36 hours for placebo, P=0.0331), and the lower dose separated after 7 days (-7.28 versus 1.59 hours, P=0.0486).

Those improvements were sustained through the second and third weeks of therapy, and throughout the rest of the study, the researchers said.

When looking only at moderate or severe headache, both treatments significantly decreased headache days compared with placebo during the second week of treatment, they added.

"These data offer a glimpse of how quickly preventive treatment effects may occur for CGRP monoclonal antibodies in [chronic migraine]," the authors wrote, adding that the early onset of effect may help with medication compliance. It may also help scientists understand the pathophysiology of migraine, they said.

The study authors wrote that the study's biggest limitation was the fact that they didn't follow up with patients to determine whether the early onset effect was clinically meaningful.

In an accompanying commentary, Volker Limmroth, MD, PhD, of the Klinik fur Neurologie und Palliativmedizin in Cologne in Germany, pointed out that the authors don't have the evidence to determine the meaningfulness of reducing a few headache hours per week and how that would benefit patients' lives.

But he stressed that the study results were still important to a better understanding of migraine, and that other types of pain may be able to be treated with similar drugs.

Treatments specifically designed to prevent migraine have until now remained elusive, said Noah Rosen, MD, director of Northwell Health's Neuroscience Institute in Great Neck, N.Y., and who was not involved in the study.

Rosen said people with chronic migraine take blood pressure medications, antidepressants, and antiseizure medications to prevent migraines, but these drugs weren't designed to treat migraine, they don't work for everyone, and can come with side effects.

"While the results are preliminary, this may be revolutionary," he said. "Many people stop their treatments early due to frustration, or reluctance to take a medicine every day. This new drug requires further investigation, but may represent the hope for a fast, tolerable, and effective treatment that migraine sufferers have been waiting for."

Enrollment for two phase III trials of TEV-48125 is currently underway.

Bigal and several of the other study authors at Teva employees. Some authors have received support of some kind from other pharmaceutical companies.

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